chr3-186641148-C-T

Variant names:

• chr3-186641148-C-T
• rs143032930
• NM_014375.3:c.336+8C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014375.3(FETUB):​c.336+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,571,710 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (24 hom.)
• Consequence: FETUB NM_014375.3 splice_region, intron
• Scores: Splicing: ADA: 0.0004438
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.341
• Publications: 0 publications found

Genes affected

FETUB (HGNC:3658): (fetuin B) The protein encoded by this gene is a member of the fetuin family, part of the cystatin superfamily of cysteine protease inhibitors. Fetuins have been implicated in several diverse functions, including osteogenesis and bone resorption, regulation of the insulin and hepatocyte growth factor receptors, and response to systemic inflammation. This protein may be secreted by cells. [provided by RefSeq, Jul 2008]

HRG-AS1 (HGNC:55915): (HRG and FETUB antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 3-186641148-C-T is Benign according to our data. Variant chr3-186641148-C-T is described in ClinVar as Benign. ClinVar VariationId is 775933.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00771 (1173/152236) while in subpopulation AFR AF = 0.0269 (1117/41546). AF 95% confidence interval is 0.0256. There are 13 homozygotes in GnomAd4. There are 554 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014375.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FETUB	NM_014375.3	MANE Select	c.336+8C>T		splice_region intron	N/A	NP_055190.2	Q9UGM5-1
	FETUB	NM_001375587.2		c.336+8C>T		splice_region intron	N/A	NP_001362516.1	Q9UGM5-1
	FETUB	NM_001308077.4		c.225+463C>T		intron	N/A	NP_001295006.1	Q9UGM5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FETUB	ENST00000265029.8	TSL:1 MANE Select	c.336+8C>T		splice_region intron	N/A	ENSP00000265029.3	Q9UGM5-1
	FETUB	ENST00000450521.5	TSL:1	c.336+8C>T		splice_region intron	N/A	ENSP00000404288.1	Q9UGM5-1
	FETUB	ENST00000382136.3	TSL:1	c.225+463C>T		intron	N/A	ENSP00000371571.3	Q9UGM5-2

Frequencies

GnomAD3 genomes AF: 0.00765 AC: 1163 AN: 152118 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00190 AC: 459 AN: 242026 AF XY: 0.00133

Gnomad AFR exome AF: 0.0268

Gnomad AMR exome AF: 0.000890

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000168

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000184

Gnomad OTH exome AF: 0.00151

GnomAD4 exome AF: 0.000834 AC: 1184 AN: 1419474 Hom.: 24 Cov.: 24 AF XY: 0.000688 AC XY: 487 AN XY: 708356

African (AFR) AF: 0.0313 AC: 1019 AN: 32586

American (AMR) AF: 0.00111 AC: 49 AN: 44124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25762

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39430

South Asian (SAS) AF: 0.0000828 AC: 7 AN: 84556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.000700 AC: 4 AN: 5716

European-Non Finnish (NFE) AF: 0.0000112 AC: 12 AN: 1075266

Other (OTH) AF: 0.00151 AC: 89 AN: 58898

GnomAD4 genome AF: 0.00771 AC: 1173 AN: 152236 Hom.: 13 Cov.: 32 AF XY: 0.00744 AC XY: 554 AN XY: 74426

African (AFR) AF: 0.0269 AC: 1117 AN: 41546

American (AMR) AF: 0.00288 AC: 44 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68004

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00694 Hom.: 20

Bravo AF: 0.00902

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.7
DANN	Benign	0.65
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00044
dbscSNV1_RF	Benign	0.066
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs143032930; hg19: chr3-186358937;